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Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including intra-uterine fetal death and intra-uterine growth retardation. In the LPS model, tumor necrosis factor alpha (TNF-alpha) is the major mediator leading to intra-uterine fetal death and intra-uterine growth retardation. Interleukin (IL)-10 protects rodents against LPS-induced intra-uterine fetal death and intra-uterine growth retardation. Melatonin is an immunomodulator. In the present study, we investigated the effect of maternally administered melatonin on LPS-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver and fetal brain. The time pregnant mice were injected with melatonin [5.0 mg/kg, intraperitoneal (i.p.)] 30 min before LPS (500 microg/kg, i.p.) on gestational day 17. As expected, TNF-alpha, IL-1beta, IL-6 and IL-10 were obviously increased in maternal serum and amniotic fluid in response to LPS. In addition, maternal LPS exposure significantly increased the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in fetal liver, and TNF-alpha and IL-10 in fetal brain. Melatonin pretreatment significantly attenuated LPS-evoked elevation of TNF-alpha in maternal serum. On the contrary, melatonin aggravated LPS-induced increase in IL-10 in maternal serum. Melatonin had no effect on LPS-evoked IL-1beta and IL-6 in maternal serum and amniotic fluid. Interestingly, maternally administered melatonin also significantly attenuated LPS-evoked elevation of TNF-alpha in fetal brain, whereas the indole aggravated LPS-induced increase in IL-10 in fetal liver. Taken together, these results indicate that maternally administered melatonin differentially regulates LPS-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain.

Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, fetal death and growth retardation, and preterm delivery. In the present study, we showed that an ip injection with LPS daily from gestational day (gd) 8 to gd 12 resulted in the incidence of external malformations. The highest incidence of malformed fetuses was observed in fetuses from dams exposed to 20 microg/kg LPS, in which 34.9% of fetuses per litter were externally malformed. In addition, 17.4% of fetuses per litter in 30 microg/kg group and 12.5% of fetuses per litter in 10 microg/kg group were externally malformed. Importantly, external malformations were also observed in fetuses from dams exposed to only two doses of LPS (20 microg/kg, ip) on gd 8, in which 76.5% (13/17) of litters and 39.1% of fetuses per litter were affected. LPS-induced teratogenicity seemed to be associated with oxidative stress in fetal environment, measured by lipid peroxidation, nitrotyrosine residues, and glutathione (GSH) depletion in maternal liver, embryo, and placenta. alpha-Phenyl-N-t-butylnitrone (PBN, 100 mg/kg, ip), a free radical spin-trapping agent, abolished LPS-induced lipid peroxidation, nitrotyrosine residues, and GSH depletion. Consistent with its antioxidant effects, PBN decreased the incidence of external malformations. Taken together, these results suggest that reactive oxygen species might be, at least partially, involved in LPS-induced teratogenesis.

Effective quantification of visitation is important for understanding many impacts of the COVID-19 pandemic on national parks and other protected areas. In this study, we mapped and analyzed the spatiotemporal patterns of visitation for six national parks in the western U.S., taking advantage of large mobility records sampled from mobile devices and released by SafeGraph as part of their Social Distancing Metric dataset. Based on comparisons with visitation statistics released by the U.S. National Park Service, our results confirmed that mobility records from digital devices can effectively capture park visitation patterns but with much finer spatiotemporal granularity. In general, triggers of visitation changes corresponded well with the parks’ management responses to COVID-19, with all six parks showing dramatic decreases in the number of visitors (compared to 2019) beginning in March 2020 and continuing through April and May. As restrictions were eased to promote access to the parks and the benefits associated with outdoor recreation, visitation in 2020 approached or even passed that from 2019 by late summer or early autumn at most of the parks. The results also revealed that parks initially saw the greatest increases in visitation after reopening originating from nearby states, with visitorship coming from a broader range of states as time passed. Our study highlights the capability of mobility data for providing spatiotemporally explicit knowledge of place visitation.

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